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M. Triana, D. Logan, R. Jones, III, E. Delbono, J.L. Wiggs; Distribution of DNA Sequence Variants in COL8A1 and COL8A2 in Glaucoma Patients With Thin CCT . Invest. Ophthalmol. Vis. Sci. 2006;47(13):185.
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© ARVO (1962-2015); The Authors (2016-present)
Collagen VIII is a major component of Descemet’s membrane, and is composed of two subunits, Col8a1 and Col8a2 which form homotrimers. Recent studies in mice have indicated that targeted inactivation of the genes encoding the Col8a1 and Col8a2 subunits (COL8A1 and COL8A2) results in dysgenesis of the anterior segment of the eye associated with a thin corneal stroma and thinned Descemet’s membrane (Hopfer et al., FASEB J 10:1232–44). Recent studies have also indicated that central corneal thickness (CCT) is a risk factor for glaucoma and that central corneal thickness is highly heritable in the human population. The purpose of this study is to evaluate COL8A1 and COL8A2 as candidate genes for thin CCT by determining if DNA sequence variants in COL8A1 and COL8A2 are associated with thin corneas in human patients with glaucoma.
For the pilot study, all of the coding and flanking intron sequence of the COL8A1 gene and the COL8A2 gene was screened for DNA sequence variants by direct genomic sequencing after PCR amplification. 14 glaucoma patients with CCT < 500 µm were screened for sequence variants in COL8A1 and COL8A2. In addition, 14 glaucoma patients with CCT >560 µm, were screened for sequence variants in COL8A2.
The mean CCT of subjects with CCT < 500 µm was 494.9 ± 8.3 µm and the mean CCT of subjects with CCT > 560 µm was 592.8 ± 21.4 µm. There were no significant differences in CCT between the right and left eyes. DNA sequence variants in the COL8A1 gene were not found in any of the initial 14 patients with CCT < 500 µm. Screening of the COL8A2 gene, however, identified two missense changes, R155Q and P678L in 2 of the 14 patients with CCT < 500 µm. These changes were not found in the 14 patients with CCT > 560 µm. Both of these missense changes are evolutionarily conserved.
These results suggest that DNA sequence variants in the COL8A2 gene may be associated with thin corneas in some glaucoma patients. Interestingly, the R155Q missense mutation was found in the patient with the thinnest CCT. Missense changes in COL8A2 have also been found to be associated with Fuch’s corneal dystrophy and posterior polymorphous dystrophy. Descemet’s membrane has been shown to be thinned and disrupted in both of these disorders. Evaluation of the COL8A2 gene in a larger population of patients with thin and thick CCT is necessary before the role of this gene in corneal thickness can be established, and these studies are currently underway.
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